Glaucoma is a disease characterized by an increase in the intraocular pressure (IOP) often associated with optic nerve damage and visual field defect. If left untreated, glaucoma can ultimately lead to blindness.
Prostaglandins, such as prostaglandin F2alpha and its phenyl-substituted analogues, have been shown to effectively reduce the IOP in man and animals. In fact, they have been used in ophthalmic preparations in order to treat glaucoma. For instance, latanoprost is available in the form of a topical eye solution (eyedrops) and sold under the trademark Xalatan®.
Indeed, latanoprost is a potent prostaglandin F2alpha analogue which has been developed for the treatment of glaucoma. Its chemical name is isopropyl—(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]-cyclopentyl]-5-heptenoate, its molecular formula is C26H40O5 and its chemical structure is:

Specifically, latanoprost is a lipophilic prodrug in which the carboxylic acid moiety in the α-chain has been esterified to increase the bioavailability of the active drug into the eye. In addition, latanoprost is absorbed through the cornea where the isopropyl ester prodrug is hydrolyzed to the acid form to become biologically active.
Some ophthalmic prostaglandins, such as bimatoprost, latanoprost or travoprost, have also been described as being capable of promoting eyelash growth. Such prostaglandins could therefore be used for the topical treatment of eyelash hypotrichosis.
The problem generally encountered with prostaglandins is that they may be chemically unstable. In particular, latanoprost is known to be very sensitive towards light and heat. Indeed, these two elements (i.e. light and heat) may have an impact on the stability of latanoprost by provoking its hydrolyzation and/or oxidation. Consequently, unopened bottles of Xalatan® should be stored in the dark and under refrigeration at 2-8° C.
Consequently, there is a need for prostaglandin formulations which show an enhanced chemical stability of the prostaglandin and, in particular, an enhanced stability overtime towards light and heat.
The Applicant already conceived prostaglandin emulsions, and found that emulsions were a suitable vehicle to stabilize prostaglandins (see for example WO2007/042262).
However, the Applicant realized that cationic emulsions containing cationic agent, preferably quaternary ammonium halides could be unsuitable to patients having an intolerance to this ingredient. This intolerance to quaternary ammoniums is related to corneal and conjunctival lesions. These lesions may be due to dry eye syndrome, allergy, injury, cataract surgery, refractive surgery with LASIK, chemical burn, traumatism, irritation, bacterial, fungal or viral infection or side effects of some medication. A corneal or conjunctival lesion is a local destruction of corneal, conjunctival or goblet cells. Such lesions may be local or disseminated and result in corneal erosion, punctuate keratopathy, epithelial defects, corneal ulceration, corneal scarring, corneal thinning, corneal perforation, keratitis, conjunctivitis, wounds, tiny abrasions, etc. These lesions are harmful and very painful. Symptoms of these lesions may be dryness, burning and a sandy-gritty eye irritation. Symptoms may also be described as itchy, scratchy, stingy or tired eyes. Other symptoms are ocular pain, redness, a pulling sensation, and pressure behind the eye. The damage to the eye surface increases discomfort and sensitivity to bright light. The Applicant thus sought for emulsions free of cationic ingredients. Whereas the Applicant thought that cationic ingredients could play a role in stabilizing prostaglandin, it is showed in this invention that, surprisingly, an emulsion containing prostaglandin and free of cationic agent is stable overtime. The Applicant excluded cationic surfactants, and directed the search to non-ionic surfactant. Surprisingly again, the use of non-ionic surfactants leads to anionic emulsions. Without being linked to any theory, the Applicant thinks that during the manufacturing process, the emulsion released negatively charged ingredients.
This invention thus relates to an anionic emulsion made of starting components which are not negatively charged. According to an embodiment of the invention, the starting materials for the manufacturing of the invention do not include any anionic surfactants.
The present invention provides a prostaglandin composition, preferably free of cationic ingredients, which exhibits an improved stability of the prostaglandin compared to commercial products, while at the same time being non toxic, tolerable for the patient with eye surface lesions and at least as efficient as the commercially available products.